Shafi, Nimra

e18536 Background: Nucleophosmin 1 (NPM1) mutation is traditionally associated with a favorable prognosis in acute myeloid leukemia (AML), leading to classification of these patients within the European LeukemiaNet (ELN) favorable risk group. However, emerging evidence indicates that co-occurring secondary-type mutations (STMs), including ASXL1 , RUNX1 , EZH2 , and SRSF2 , may substantially modify this prognosis. While meta-analyses have quantified the relative risk associated with STMs using hazard ratios, the corresponding absolute survival impact remains unclear, limiting clinical interpretability and decision-making. Methods: We performed meta-analysis–based projection modeling using pooled overall survival hazard ratios reported in a recent systematic review and meta-analysis of 4,022 NPM1-mutated AML patients. For the ELN-favorable subgroup, the pooled hazard ratio for overall survival associated with STMs (HR 1.95; 95% CI 1.39–2.73) was combined with externally derived baseline 5-year survival estimates under a proportional hazards framework. Absolute survival probabilities were calculated using established survival–hazard transformations, and results were translated into projected outcomes for a hypothetical cohort of 1,000 future ELN-favorable NPM1-mutated AML patients. Uncertainty was quantified using the meta-analytic confidence interval. Results: Assuming a baseline 5-year overall survival of 70% for ELN-favorable NPM1-mutated AML patients without STMs, the presence of STMs was projected to reduce 5-year survival to approximately 50%. Based on the confidence interval of the pooled hazard ratio, projected survival with STMs ranged from 38% to 61%. In a simulated cohort of 1,000 patients, this corresponds to approximately 300 deaths at 5 years in the absence of STMs versus 501 deaths in the presence of STMs, yielding an estimated 200 excess deaths per 1,000 patients (plausible range: 90–320 excess deaths). These findings were robust across visualizations including absolute survival projections, stacked outcome distributions, and excess mortality estimates. Conclusions: Meta-analysis–based projection modeling demonstrates that secondary-type mutations may negate much of the favorable prognosis traditionally attributed to ELN-favorable NPM1-mutated AML, translating into a large absolute survival decrement in future patient cohorts. Converting relative risk estimates into absolute survival and event projections provides clinically actionable insight and supports the incorporation of secondary-type mutation status into risk stratification, trial design, and therapeutic decision-making.

ABSTRACT Background Atrial fibrillation (AF) is a prevalent arrhythmia that frequently coexists with cardiomyopathy, leading to deteriorated cardiovascular outcomes. Analyzing the trends associated with these conditions is essential for improving prevention strategies and management practices. Methods CDC WONDER (1999–2023) data were analyzed to assess AF with cardiomyopathy‐related mortality in patients aged ≥ 25. Using Joinpoint regression analysis, we calculated age‐adjusted mortality rates (AAMRs) per 100,000 patients and average annual percentage changes (AAPCs) to analyze mortality trends. Results AF with cardiomyopathy is responsible for 126,377 deaths among adults aged 25 and older. Alarmingly, AAMRs have surged from 1.8 per 100,000 in 1999 to 3.0 in 2023 (AAPC: 2.11, p < 0.001). The upward trend remains pronounced, particularly between 2016 and 2021, with an annual percentage change of 6.17 ( p = 0.02). Disparities in mortality rates are striking. Men face a higher AAMR than women (3.1 vs. 1.5), and Black individuals bear the heaviest burden at 2.4, closely followed by Whites at 2.3. Regionally, Vermont stands out with the highest AAMR at 3.6, while New York reports the lowest at 1.3. Both rural and urban areas maintain equal AAMRs of 2.1, yet the increase in rural regions is particularly concerning, reflecting an AAPC of 2.44 compared to 1.78 in urban settings. Conclusion The rising mortality rates from AF with cardiomyopathy in patients, particularly among men, Black individuals, and rural residents, demand urgent action. These concerning trends underscore a public health crisis that must be addressed.